The overall long-term objective of this project is to incorporate clinical decisions through interactive feedback into the inverse treatment planning process for intensity-modulated radiotherapy. The hypotheses are that this will (i) make the inverse planning process more effective and (ii) increase the clinical relevancy of optimized plans, introducing better tradeoffs between target coverage and sparing of healthy tissues. The new approaches to tackle this problem include multi-criteria optimization techniques and an interactive plan navigation tool for searching a pre-calculated treatment plan database. The idea of multi-criteria optimization in treatment planning is that multiple planning criteria in different critical structures and in the target volume can be controlled simultaneously. In contrast, in current inverse planning algorithms a single objective (score function) is maximized or minimized. This conventional optimization gives only limited control of the planning result, and major manual plan tweaking using trial and error is often necessary. In the previous funding period the feasibility of the approach has been demonstrated in theoretical example cases and retrospective treatment planning studies. This showed the potential of the multi-criteria planning approach and a potential for improvement in some areas. The first aim of the current project is to improve the usability of the method. This will include a reduction of the dimensionality of the problem, to make the tradeoff decision easier and faster for the clinician. It will also include the generation of plan databases with minimal user intervention, and developments of the plan navigation approach. The second aim is to extend functionality. Hardware and delivery aspects will be incorporated. A means to interactively optimize beam orientations will be provided. Dose conformality will be included in the tradeoff discussion, and the user will be able to make tradeoff decisions based on alternative biologically motivated criteria. Finally, in aim 3, the hypothesis that the multi-criteria planning paradigm will lead to better treatment plans in less time will be tested in the clinic. This work has the potential to lead to clinically more suitable and more individualized radiation treatment plans, with better dose coverage of the tumor target volume and/or reduced radiation dose to surrounding healthy tissues. Furthermore, shorter treatment planning times will reduce the overall cost. PUBLIC HEALTH RELEVANCE: This work has the potential to lead to clinically more suitable and more individualized radiation treatment plans, with better dose coverage of the tumor target volume and/or reduced radiation dose to surrounding healthy tissues. Furthermore, shorter treatment planning times will reduce the overall cost.